Frequency of Acquired Renal Cystic Disease in Patients on Long-Term Hemodialysis and Associated Renal Cell Carcinoma

Background Acquired cystic renal disease is one of the complications of end-stage renal disease (ESRD) patients on dialysis. We aimed to define the prevalence of acquired cystic renal disease in a dialysis center in a tertiary care setup in Pakistan. Materials and methods We conducted a cross-sectional study of 246 patients with ESRD from October 1, 2017, to March 30, 2018. We collected patient demographic data, comorbidities, duration (years), frequency (sessions/week), length of each dialysis session (hours), ultrasound findings, cystic renal disease occurrence, and associated complications for analysis. Results Our patient population consisted of 115 women (46.7%) and 131 men (53.3%) and had a mean age of 55.9 ± 15.1 years. Thirty-seven patients were on dialysis for one year, 78 (31.7%) for two years, and 131 (53.3%) for three or more years, as its more common with increasing duration. The mean dialysis duration was 2.3 ± 0.7 years. Of 246 patients, 49 (19.9%) had acquired cystic renal disease. Conclusions Given improved health care facilities, an increasing number of patients have a good survival on dialysis and develop long-term complications associated with end-stage renal disease, such as acquired cystic renal disease. Because the acquired renal cystic disease is associated with renal cell carcinoma, physicians should evaluate dialysis patients for renal cell carcinoma, especially after three to five years of dialysis.


Introduction
Pakistan's annual incidence of end-stage renal disease (ESRD) is estimated to be approximately 100 cases per million people [1]. Patients with ESRD experience several acute and chronic complications, including acquired cystic renal disease (ACRD). ACRD refers to the bilateral development of renal cysts in patients with ESRD caused by a primary non-cystic renal disorder [2]. The physical environment of chronic uremia in ESRD patients might facilitate cell division and inhibit apoptosis, leading to cyst formation and ACRD [3]. ACRD has been associated with a greater duration of dialysis; thus, in recent years, the incidence of ACRD has increased due to the longer survival of patients on dialysis [4]. ACRD is not associated with pain, unlike autosomal dominant polycystic kidney disease (ADPKD), but it is associated with a greater risk of cancer [5]. ACRD-associated renal cell carcinoma (RCC) is the most common tumor subtype in ESRD patients. This is especially concerning because the ESRD population has an up to 50 times greater risk of developing RCC than the healthy population [6]. Screening and early detection of dialysis patients every three years with computed tomography (CT) or ultrasound to detect ACRD can increase the life expectancy of patients with ESRD by one-and-a-half-years-a strategy that may be considered helpful in younger and healthier patients with fewer comorbidities than older patients [4]. The prevalence of ACRD increases with the duration of dialysis; approximately 90% of patients on dialysis for more than nine years have ACRD, 40% to 60% of patients on dialysis for more than five years have ACRD, and 20% of patients on dialysis for one to three years have ACRD [2]. No patients on dialysis for less than one year developed ACRD in the Pakistani population [7]; however, the sample size of that study was small, and most patients did not use dialysis for more than one year. There was no clinical or sonological evidence of RCC in these patients, and the prevalence of ACRD was 20.8% (18.9% in men and 22.6% in women). However, there is minimal data available from Pakistan regarding the prevalence of ACRD in patients on dialysis for more than one year. Therefore, we conducted this study to assess the current disease burden of ACRD in hemodialysis patients in the nephrology department of Shifa International Hospital in Islamabad.

Materials And Methods
We conducted a cross-sectional study of patients treated at the dialysis unit of the Department of Nephrology, Shifa International Hospital in Islamabad, from October 1, 2017, to March 30, 2018. The study included men and women aged 18 to 70 years diagnosed with ESRD and receiving dialysis for longer than one year. We excluded any patients with known diagnosis of ADPKD, multiple cystic diseases, and previous ultrasound demonstrating cystic disease before the onset of dialysis from their available imaging studies. Furthermore, no patient had genetic testing for diagnosis. This study was approved by the Institutional Review Board (IRB) and Ethics Committee (EC) of Shifa International Hospital with approval number IRB# 645-093-2016. All participants provided written informed consent prior to data collection.
We collected detailed history, including age, sex, frequency and duration of dialysis, and length of each dialysis session. Patients underwent an ultrasonography examination of their kidneys, ureters, and bladders. We then assigned patients into three groups according to dialysis duration of one year, two years, or three or more years. We then noted the presence or absence of ACRD in each group. We used IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp to analyze our results, and p<.001 was considered statistically significant.

Results
The study population consisted of 246 participants with a mean age of 55.   Table 2). Only one patient had ACRD in the one-year dialysis group, and one patient had ACRD in the twoyear dialysis group. Among the patients receiving dialysis for three or more years, 47 patients had ACRD (p<.001).  Among the 49 patients with ACRD, 32 (65.4%) were men, and 17 (34.6%) were women (p=0.059). ACRD was present in 39 patients receiving twice-weekly dialysis and 10 patients receiving thrice-weekly dialysis (p=0.003). Among those with ACRD, 14 had kidneys smaller than 7 cm, 30 patients had a kidney size of 7 cm to 9 cm, and five had a kidney measuring 10 cm to 12 cm ( Table 3). We stratified patients by age and found that ACRD was present in two patients younger than 20 years, three patients aged 21 to 40 years, 18 patients aged 41 to 60 years, 25 patients aged 61 to 80 years, and one patient older than 80 years (

Discussion
To the best of our knowledge, this study represents the most extensive study to assess the presence of ACRD in a Pakistani population. ACRD was first described by Dunnil et al. in 1977 [8]. The condition is characterized by three or more cysts per kidney in a patient on dialysis without a hereditary cause of cystic diseases such as autosomal dominant polycystic kidney disease or tuberous sclerosis. Within the first three years of dialysis, approximately 10% to 20% of patients develop ACRD. By five years of dialysis, 40% to 60%